马来酸噻吗洛尔原料和滴眼剂中对映体杂质的含量测定

目的：了解国内生产的马来酸噻吗洛尔及其滴眼液中对映体杂质含量，为我国药典制订手性药物杂质限量提供参考数据。方法：应用手性高效液相色谱法，色谱条件为：Chiralcel OD 手性柱（4.6 mm×150 mm，5μm）；检测器波长297 nm；流动相为正己烷-异丙醇-二乙胺（480∶20∶1）；柱温25 ℃；流速1.0 ml/min，进样量5 μl。结果：两个对映体的色谱分离度为4.3。不同厂家的两批马来酸噻吗洛尔原料药中的对映体杂质平均含量小于0.67%，3批马来酸噻吗洛尔滴眼液中的对映体杂质平均含量小于0.31%。结论：各批马来酸噻吗洛尔产品中对映体杂质含量均符合欧洲药典标准,我国药典可以参照此数据。

Determination of enantiomeric impurity of timolol maleate in bulk substances and eye drops

Objective： To determine the enantiomeric impurity contents of domestic timolol maleate in bulk drugs and eye drops.Methods： Enantiomer impurity of timolol was assayed by chiral high performance liquid chromatography. The chromatographic conditions were as follows: chiralcel OD chiral column (4.6 mm ×150 mm, 5μm), detection wavelength: 297 nm, mobile phase: hexane-isopropanol-diethylamine (480∶20∶1), column temperature: 25 ℃, flow rate: 1.0 ml/min, sample injection volume: 5 μl.Results： The resolution between R- and S-timolol was more than 4. The enantiomeric impurity contents were less than 0.67% on average in two batches of timolol maleate bulk drugs, and 0.31% on average in three batches of timolol maleate eye drops.Conclusion： Enantiomeric impurity contents in each batch of products all meet European Pharmacopoeia criteria, which can be used as references in Chinese Pharmacopoeia criteria.